We investigate the evolution of co-occurring analogous enzymes involved in L-tryptophan and L-histidine biosynthesis in Actinobacteria. Phylogenetic analysis of trpF homologues, a missing gene in certain clades of this lineage whose absence is complemented by a dual-substrate HisA homologue, termed PriA, found that they fall into three categories: (i) trpF-1, an L-tryptophan biosynthetic gene horizontally acquired by certain Corynebacterium species; (ii) trpF-2, a paralogue known to be involved in synthesizing a pyrrolopyrrole moiety and (iii) trpF-3, a variable non-conserved orthologue of trpF-1. We previously investigated the effect of trpF-1 upon the evolution of PriA substrate specificity, but nothing is known about the relationship between trpF-3 and priA. After in vitro steady-state enzyme kinetics we found that trpF-3 encodes a phosphoribosyl anthranilate isomerase. However, mutation of this gene in Streptomyces sviceus did not lead to auxothrophy, as expected from the biosynthetic role of trpF-1. Biochemical characterization of a dozen co-occurring TrpF-2 or TrpF-3, with PriA homologues, explained the prototrophic phenotype, and unveiled an enzyme activity trade-off between TrpF and PriA. X-ray structural analysis suggests that the function of these PriA homologues is mediated by non-conserved mutations in the flexible L5 loop, which may be responsible for different substrate affinities. Thus, the PriA homologues that co-occur with TrpF-3 represent a novel enzyme family, termed PriB, which evolved in response to PRA isomerase activity. The characterization of co-occurring enzymes provides insights into the influence of functional redundancy on the evolution of enzyme function, which could be useful for enzyme functional annotation.
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The biological dimer of MurIMtb shown as a protein cartoon. Interface residues that form hydrogen bonding interactions or salt links are highlighted in purple and yellow. For further details see pp. 1267-1280. Image kindly provided by Kurt Krause. - PDF Icon PDF LinkFront Matter
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Research Article|
April 26 2016
Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop
Ernesto A. Verduzco-Castro;
Ernesto A. Verduzco-Castro
*Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, CP36821, México
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Karolina Michalska;
Karolina Michalska
†Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
‡Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
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Michael Endres;
Michael Endres
†Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
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Ana L. Juárez-Vazquez;
Ana L. Juárez-Vazquez
*Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, CP36821, México
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Lianet Noda-García;
Lianet Noda-García
1
*Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, CP36821, México
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Changsoo Chang;
Changsoo Chang
†Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
‡Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
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Christopher S. Henry;
Christopher S. Henry
§Mathematics and Computer Science, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
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Gyorgy Babnigg;
Gyorgy Babnigg
†Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
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Andrzej Joachimiak;
Andrzej Joachimiak
†Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, Illinois 60439, U.S.A.
║Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, U.S.A.
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Francisco Barona-Gómez
Francisco Barona-Gómez
2
*Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, CP36821, México
2To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 14 2015
Revision Received:
February 23 2016
Accepted:
February 29 2016
Accepted Manuscript online:
February 29 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (9): 1141–1152.
Article history
Received:
December 14 2015
Revision Received:
February 23 2016
Accepted:
February 29 2016
Accepted Manuscript online:
February 29 2016
Citation
Ernesto A. Verduzco-Castro, Karolina Michalska, Michael Endres, Ana L. Juárez-Vazquez, Lianet Noda-García, Changsoo Chang, Christopher S. Henry, Gyorgy Babnigg, Andrzej Joachimiak, Francisco Barona-Gómez; Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop. Biochem J 1 May 2016; 473 (9): 1141–1152. doi: https://doi.org/10.1042/BJ20151271
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